Lactobacilli function as microbicides in the human vagina through production of H202, acids and other products which inhibit the survival and/or growth of genital pathogens. The goal of the proposed project is to evaluate the efficacy of a Lactobacillus suppository in colonizing the vagina, normalizing the vaginal ecosystem (decreasing vaginal pH, suppressing other pathogens), and decreasing acquisition of bacterial vaginosis and Niessena gonorrhoeae. Earlier work conducted as part of the University of Washington STD CRC has shown that lack of vaginal lactobacilli increases the risk of gonorrhea (OR=4.6) and bacterial vaginosis (OR-15.2). Factors associated with lack of vaginal lactobacilli include nonwhite race, having multiple sexual partners, and regular douching. Longitudinal cohort data supports the association between lack of vaginal lactobacilli and acquisition of gonorrhoeae and bacterial vaginosis. A lactobacillus vaginal suppository has been developed and shown to colonize women. The proposed study is a double-blinded, placebo-controlled trial of a Lactobacillus suppository in 924 adolescent girls attending an inner-city clinic. Girls will be followed at 4-month intervals for 1 year. The presence of genital tract infection and vaginal lactobacilli will be determined at baseline and each follow-up visit. The hypothesis is that sustained use of exogenous lactobacilli intravaginally will decrease acquisition of genital tract infections including gonorrhea and bacterial vaginosis. The specific aims are 1) to assess the relationship between genital infection and lack of lactobacilli in a population of predominantly nonwhite adolescent girls; 2) to determine the frequency of behaviors associated with lack of lactobacilli (multiple partners; douching) at baseline; 3) to assess the effect of the Lactobacillus suppository on the vaginal ecosystem (vaginal pH, lactobacilli, other microorganisms); 4) to determine whether women randomized to receive the Lactobacillus suppository have decreased acquisition of bacterial vaginosis and gonorrhea compared to placebo-treated women after accounting for potentially confounding behaviors; 5) to evaluate the effect of the Lactobacillus suppository on acquisition of other infections including chlamydia, trichomoniasis, vulvovaginal candidiasis, urinary tract infections and pelvic inflammatory disease; and 6) to assess the demographic, behavioral and microbiologic factors associated with loss or acquisition of H202-producing and H202-negative lactobacilli. This project will yield new information on lactobacilli as endogenous microbicides and suggest new strategies for prevention of STD's and their sequelae. This project will interact with project 6 regarding adolescent behaviors and will be supported by Clinical Core B, the Biostat/Epe Core C, and Microbiology Core D.